When Christine Piff gets up in the morning, she takes a shower, has breakfast and then cleans her face. An unremarkable procedure, except that she removes her face piece by piece before cleaning it. Afterwards, she clips it back on, puts on her make-up and gets ready to start work.
Piff had facial cancer 17 years ago. Surgery and years of radiotherapy have left her with a hollow from her left eyebrow to the jaw bone below. The severity of the disfigurement means reconstructive surgery is unlikely to work and a false face or prosthesis is the most likely solution. But over the years, prostheses have proved troublesome. Like many other patients, she was given one attached to her glasses over the bridge of the nose. It was uncomfortable, Piff says, but worse still: ‘It meant that when I took my glasses off my face came off with them.’ She tried a lighter prosthesis stuck on with glue, but it fell off the first time she used it. She went back to the glasses attachment.
Three years ago, Piff had five titanium screws implanted in the remaining bone of her face. The heads of the screws protrude through the skin and, in a second operation, tiny titanium posts were attached to each one. Three separate prostheses clip onto the titanium posts with fasteners like press studs. The cosmetic effect is so good that even fairly close acquaintances are unaware that half of her face comes off at night.
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NATURAL BONDING
The key to the success of Piff’s prosthesis is the interaction between natural bone and titanium. Bone grows into the titanium screws and secures them so that the base for the prostheses is firm. This bond between implant and bone, so-called osseointegration, is being actively studied throughout the world. Researchers believe that increased knowledge of titanium and other materials, and the body’s reaction to them, will make permanent surgical implants the norm. This could herald a new era of dental and orthopaedic work, with immediate applications in dentistry, reconstructive surgery, and hip, knee, finger and ankle replacements.
The story of osseointegration began with an accidental discovery forty years ago. A young Swedish scientist, Per-Ingvar Branemark, was studying the function of blood and marrow, and wanted to be able to see inside the fibula bone in a rabbit’s leg. He made a viewing chamber by screwing a cylinder of titanium into the fibula. Titanium is a lightweight metal that is resistant to corrosion even in hostile environments such as the body of a rabbit, and Branemark was able to watch the marrow making blood cells. On completing his study, however, he was irritated to discover that bone had grown into the threads of the titanium cylinder so that he was unable to remove the expensive equipment.
A few years later, Branemark was studying the effects of eating, drinking and smoking on blood cells, and developed a tiny titanium viewing chamber which he inserted into a fold of soft tissue in the upper arm of medical student volunteers. The chambers were left in place for months as the study proceeded and caused no adverse reaction. Only then did it occur to Branemark that a metal which could form such a strong bond with bone, without triggering a reaction from the body’s immune system, could be extremely useful in surgery.
He was soon able to act on this finding. In 1965, Branemark’s team operated on a man born with deformed chin and jaw, who could neither eat nor speak normally. They inserted titanium screws and posts into his mouth and attached a set of dentures. Almost three decades later, the teeth are still in action.
Branemark, now professor of applied biotechnology at the University of Gothenburg, and his group have since installed a million titanium fixtures in 300 000 patients, some with deformities, others with severe dental problems. Ninety-five per cent of prostheses in the upper jaw have been successful, and 99 per cent of those in the lower jaw.
The biocompatibility of titanium, or the body’s lack of reaction to it, is due to the stable and unreactive layer of oxide that forms on its surface. If the metal is scratched with a sharp instrument, the oxide layer ‘self-repairs’ in nanoseconds, even when surrounded with saline or bodily fluids, according to Tomas Albrektsson, professor of biomaterials at the University of Gothenburg. With most implants, the body’s immune system reacts to the material after surgery, stimulating fibrous repair. Titanium, with its oxide layer, does not provoke a reaction from the immune system, allowing normal bone repair to take place so that there is a secure bond between implant and bone.
The technique of using titanium posts as a base for prostheses and other attachments is being eagerly adopted by other specialists. People who have lost ears or noses through disease, accident or congenital malformation have had replacements clipped on in the same way as Piff’s facial prosthesis. Hearing aids can be attached to titanium posts on the side of the head for people unable to wear a conventional aid because of skin allergies or inflammation or infection within the ear. Surgeons operating on cleft palates graft bone, taken from the pelvis, into the cleft. In a later operation, they put titanium implants into the grafted bone. Artificial crowns and dentures can then be fixed to the titanium posts.
SLOW PROGRESS
But the progress with osseointegration in the head has not been matched in other parts of the body, such as replacement hips and knee joints. The reason is that while titanium is a strong metal, it is too soft for such weight-bearing joints.
At the last estimate, the NHS provides 40 000 hip replacements and 16 000 knee replacements a year in Britain, and more are carried out in the private sector. In the US, the figures are 123 000 hip replacements and 95 000 knees. Most are carried out in the time-honoured way of cementing in a replacement joint, usually made of stainless steel (see ‘Steel and cement’). These give excellent results in people over 70, who can be fairly confident that their new joints will last 10 or even 15 years. But as people live longer, they are increasingly likely to need a second operation. And active patients in their 60s or younger are poorly served by current replacement joints. The stress they put on new joints means many last no more than five years.
Researchers such as Albrektsson have looked at other metals which are biocompatible, but all have disadvantages. Niobium, for example, has been used in implants but is softer than titanium. ‘I don’t think there will be metals better than titanium. We’ve looked at most of them,’ says Albrektsson. Instead, researchers are concentrating on finding ways of strengthening the interface between the artificial joint and natural bone. Osseointegration, they believe, will prove stronger than any cement that can be safely used within the body. Research aimed at improving the results is many-pronged. The materials used for making replacement joints are being re-examined. New coatings which may encourage bone to grow into implants are being developed and tested. Hormones which could stimulate bony repair are about to start clinical trials. Simultaneous bone marrow transplantation is showing promising results. New surgical procedures, including the possible use of diving chambers, are being developed.
The broad aim of most research, however, is to develop materials and techniques which will stimulate the bone-forming cells or osteoblasts to grow until the bone is in direct contact with the replacement joint.
LOOSE JOINTS
One of the most common causes of failure is the joint working loose. Bone can grow into the tiny surface irregularities on the surface of a bio-inert material, but anything on the implant which the body’s defences recognise as foreign is likely to trigger the immune system. Once this has happened, fibrous rather than bony repair is likely. Fibrous repair may also be prompted by poor surgical techniques, by certain materials or by premature loading of the new implant. An implant surrounded by fibrous tissue is able to move against the bone, and over time this movement can destabilise it, especially where the replacement joint is in an active person.
Another common problem is bone loss. In hip and knee replacements, the moving parts are usually covered with polyethylene to provide a smooth gliding surface. Constant use wears away the surface of the joints, and ‘wear particles’ of polyethylene gradually break away and build up in any gap between implant and bone. This causes inflammation, which in turn stimulates the bone-destroying cells or osteoclasts to start absorbing bone so that the implant works loose. Researchers are looking for improved gliding surfaces and surgeons are attempting to eliminate the gap between implant and bone.
Weight transfer across joints after an implant is crucial. Normal weight-bearing exercise encourages bone formation. Conversely, NASA’s work with astronauts has shown that bone loss occurs when there is no gravity, and hence no weight-bearing. After someone has received a cementless artificial hip joint, there is a slight change in the way weight is transferred across the joint. In the case of a hip replacement, this means that the upper part of the thigh bone, the femur, is shielded from stress, which can prompt bone loss.
To combat such problems, researchers are experimenting with different surfaces which may encourage early bone build-up around the upper part of the femur. This means weight is transferred more normally to this susceptible area and this in turn prevents bone loss. Rough surfaces allow bone to grow into them more actively, so one approach is to use titanium fibre mesh bonded to the top of the shaft.
An alternative approach is to coat the top of the shaft with calcium phosphates, including hydroxyapatite, to mimic natural bone (which is made of the same minerals). Hydroxyapatite is too brittle to be used as an implant itself but rather is sprayed on to the metal. Electron microscopy has shown crystals straddling bone and implant, indicating that bone and coating have bonded chemically.
It looked as if such a coating would stimulate bony repair and full osseointegration of implant into bone. But early clinical use of the hydroxyapatite coatings has been disappointing. According to Albrektsson, the problem may start when the hydroxyapatite coating breaks down, months or years after surgery. In research still to be published, one of his students examined bone formation around coated and non-coated implants. Up until six months after the operation, there was no difference in the bone formation. But four to five years later, the coated implants had only half as much bone around them. ‘We don’t know the reason. It could be that hydroxyapatite fragments with time. The fragments may attract macrophage cells which then attack the bone.’
Albrektsson believes that further research will solve these problems. His department is looking at ways of applying the coating to the implant. The traditional plasma spray gives a coating 40 to 50 micrometres deep. New techniques, such as ion beam sprays or salt gel deposition, allow scientists to apply coatings of under 10 micrometres which may reduce the amount of potentially harmful fragments around the joint and ‘could be promising’.
In London, researchers are incorporating growth hormone into the coating in an attempt to encourage osseointegration. Sandra Downs at the Royal National Orthopaedic Hospital Trust has shown that growth hormone stimulates cells which form bone, and may also prompt the release of a hormone that indirectly stimulates bone growth. She says the growth hormone can boost bone growth within two weeks, and is an easy hormone to work with because its function is not critically dependent on concentration. Clinical trials in hip replacement surgery are due to start later this year.
FORGIVING CEMENT
But the case for osseointegration may have been overstated, according to Bill Harris, professor of orthopaedic surgery at Harvard Medical School. He argues for the continuation of the present practice of cementing in hips and knees. Cement is made of polymethyl methacrylate (PMMA), a material that surgeons like because it is ‘very forgiving’ and has been used for years. It is relatively easy for a surgeon to mould the pliable material so that it is in contact with both bone and implant. But until the 1970s, long-term results were poor. Harris says this is because surgeons prepared the cement casually in the open and bubbles sometimes formed. Surgeons also simply pressed it down into the bone with their fingers. Now surgeons prepare it in a vacuum and fire it into the joint with a gun.
The change in procedure has brought about a corresponding improvement in results, he says. ‘With improved use of cement the long-term results are good. At 15 years only 2 per cent have had to be re-operated on; 98 per cent are still walking around,’ says Harris.
But cement is anathema to Albrektsson. He says it will not take the strain imposed on it by younger active patients. Also PMMA heats up spectacularly when mixed – to an average of around 70 degree C – and this causes damage to cells. Worse, he says, the cement leaks chemicals which, over time, may set up a tissue reaction. ‘People worry about amalgam in teeth. Amalgam is like a health drug compared to bone cement.’ Albrektsson concedes that many people are walking around quite happily with cement in their bones. But he says, ‘As soon as we can develop a non-cemented method which works as well we should stop using it.’
Harris also acknowledges that osseoin-tegration is important in total hip replacements. Bone loss where the socket of the joint is implanted into the pelvis is an important reason for the failure of prostheses over time. Harris has found that 9 per cent of total hip replacements fail in the long-term because of bone loss in the pelvis.
Albrektsson, meanwhile, is challenging the belief that titanium is too soft. He was encouraged by the success of the metal in dentistry and believes that ‘commercially pure’ titanium, which contains less than 0.5 per cent iron and some other elements including carbon, may be strong enough. ‘We have used titanium in oral implants for a long time and they are pretty loaded when people bite,’ he says. Over the past two years, Albrektsson has carried out a few hip replacements made with titanium alone and is monitoring patients’ progress carefully. He stresses that the work is in the early stages.
Other work at Gothenburg suggests osseointegration may be influenced by factors other than the materials used in replacement joints. One of the most common situations in which patients receive facial prostheses is following an operation to remove tumours. Many also receive radiotherapy, which damages the blood vessels that would normally nourish the bone.
According to Gasta Granstrom, oral surgeon at Sahlgrenska Hospital in Gothenburg, this prevents bone growth into the implant and reduces the chances of long-term success. In his own work, 35 per cent of implants in irradiated bone fail after 10 years. This compares with 10 per cent in normal bone. But he has achieved dramatic improvements with hyperbaric oxygen.
Patients sit in the equivalent of a diving chamber breathing oxygen at twice normal atmospheric pressure. The technique has been used for many years to treat diving accidents, carbon monoxide poisoning or difficult wounds. Patients who have received radiotherapy and are about to have implants fitted for a prosthesis have 90-minute sessions in the diving chamber for 20 days leading up to surgery and 10 days afterwards.
It is a clumsy procedure, but Granstrom says it increases the supply of oxygen to damaged bone, promoting bone formation and better healing around the implant. He has been following up patients for six years and says the failure rate is only 1.7 per cent.
Even allowing for the shorter follow-up period, these results appear to be better than the results in normal bone. Granstrom believes many patients, even those who have not had radiotherapy, could benefit from the treatment. ‘We have been discussing this and of course, if it gives better bone growth it could be worth it. But we need a better way of administering it, and it’s difficult. Oxygen can’t be given by injection, you have to breathe it in.’
Branemark believes that long-term answers to existing problems will lie in the bone itself. He has always stressed the importance of causing as little disruption as possible to bone tissue during the surgery. He routinely adds the patient’s own bone marrow, taken from part of the hip bone, to the site of the implant. It promotes bone healing and repair, he says. ‘I believe bone and marrow belong together. They function together, you can’t separate them,’ he says.
The approach may prove especially successful in arthritic finger joints, he says, in which the original disease frequently recurs after surgery. His team is replacing finger joints with titanium and adding bone marrow during the operation. Results are preliminary, but Branemark is optimistic. He argues that bone has too long been regarded as an inert tissue, when in fact gentle handling of it could vastly improve surgical results. After three decades of experience with titanium implants, ‘we are moving from carpentry to biology,’ he says.
Helen Saul is a journalist specialising in health and medical issues.
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Steel and cement
The traditional Charnley hip, made of stainless steel, was developed in the 1960s and is still widely used today. The hip joint works like a ball and socket and in a total hip replacement, surgeons cut out the patient’s own joint. The artificial socket is inserted into the pelvis, and the ‘ball’ has a shaft which is pushed right down into the patient’s thigh bone, the femur.
One of the problems with stainless steel, particularly in active patients, is that it is rigid. Gordon Blunn, deputy director of research at the Royal National Orthopaedic Hospital Trust in London, says ‘When you climb the stairs, you exert a force equivalent to four or five times your body weight. Bone does bend a little.’ This means that the bone may bend around the implant and loosen the bond between bone and implant.
A cobalt-chromium alloy is another standard artificial joint, widely used in the US and Sweden. Cobalt is more resistant to corrosion than stainless steel, and easier to cast into complex geometric shapes. Titanium, a relative newcomer, is also used as an alloy, mixed with aluminium and vanadium. Although titanium is generally considered too soft to use alone, its ‘bendiness’ even as an alloy gives it advantages in younger patients, says Blunn, allowing it to move with bone.
